An expedient, chemoselective N-chloroacetylation of aminoalcohols under metal-free bio-compatible conditions

• Main Authors: B. S. Balaji, Neha Dalal
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2018-10-01
• Series: Green Chemistry Letters and Reviews
• Subjects: Chloroacetylation; aminoalcohols; ceramides; phosphate buffer; bio-compatible synthesis
• Online Access: http://dx.doi.org/10.1080/17518253.2018.1544286

We are reporting for the first time, efficient, highly chemoselective N-chloroacetylation of amino compounds (amino alcohols, amino acids) by chloroacetyl chloride, without compromising its high reactivity, to give chloroacetamides in phosphate buffer within 20 min. We have systematically studied the effects of buffers, metal salts and HCl scavengers to optimize the reaction conditions. We have carried out intermolecular competitive reactions and shown that anilines and aliphatic amines can be selectively N-chloroacylated in the presence of alcohols and phenols. The acylated products are obtained in high yields and can be easily isolated without chromatographic separation. This reaction represents the first example of a metal-free bio-compatible synthesis under neutral conditions. This method is eco-friendly, easily scalable and robust. We have further studied the intramolecular competitive reactions of aminoalcohols and prepared various N-chloroacetamides in very good yields. Finally, this protocol was conveniently extended to ceramides synthesis as well.